Photoeradication of bacteria with porphycenes: Substituent effects on the efficiency.

Considering the world-wide problem of growing antibiotic resistance of bacteria, photodynamic inactivation (PDI) has a potential to become the treatment approach against some infectious diseases. In our study, four differently substituted porphycenes were compared in terms of their bactericidal activity against E. faecalis. All tested compounds had a similar photophysical characteristics, i.e., there were no significant differences in the location of absorption bands or molar absorption coefficients. Also, singlet oxygen generation quantum yields were very similar. Surprisingly, differently substituted porphycenes caused very diverse PDI effects. Special attention was drawn to the tert-butyl moieties. Our studies demonstrated that the presence of these substituents lowers the bactericidal potential significantly and can completely block the activity when more than one moiety is introduced to the molecule. The porphycenes lacking tert-butyl groups exhibited much higher PDI potential and we assign this effect to different interactions of the differently substituted porphycenes with the bacterial cells. Most likely, the presence of tert-butyls impairs cell penetration by the photosensitizer. These results remind that the favorable photophysical characteristics do not ensure that the compound considered as a potential PDI agent can reach the microbial cells.

Relationships among streptococci from the mitis group, misidentified as Streptococcus pneumoniae.

The aim of our study was to investigate phenotypic and genotypic features of streptococci misidentified (misID) as Streptococcus pneumoniae, obtained over 20 years from hospital patients in Poland. Sixty-three isolates demonstrating microbiological features typical for pneumococci (optochin susceptibility and/or bile solubility) were investigated by phenotypic tests, lytA and 16S rRNA gene polymorphism and whole-genome sequencing (WGS). All isolates had a 6-bp deletion in the lytA 3' terminus, characteristic for Mitis streptococc and all but two isolates lacked the pneumococcal signature cytosine at nucleotide position 203 in the 16S rRNA genes. The counterparts of psaA and ply were present in 100% and 81.0% of isolates, respectively; the spn9802 and spn9828 loci were characteristic for 49.2% and 38.1% of isolates, respectively. Phylogenetic trees and networks, based on the multilocus sequence analysis (MLSA) scheme, ribosomal multilocus sequence typing (rMLST) scheme and core-genome analysis, clearly separated investigated isolates from S. pneumoniae and demonstrated the polyclonal character of misID streptococci, associated with the Streptococcus pseudopneumoniae and Streptococcus mitis groups. While the S. pseudopneumoniae clade was relatively well defined in all three analyses, only the core-genome analysis revealed the presence of another cluster comprising a fraction of misID streptococci and a strain proposed elsewhere as a representative of a novel species in the Mitis group. Our findings point to complex phylogenetic and taxonomic relationships among S. mitis-like bacteria and support the notion that this group may in fact consist of several distinct species.

Diversity of serotypes and new cps loci variants among Streptococcus suis isolates from pigs in Poland and Belarus.

Streptococcus suis plays an important role in infections in pigs but information about the epidemiology of this pathogen in Poland and Belarus remains scarce. Ninety-six isolates from brain and lungs were studied by PCR-based serotyping, analysis of virulence-associated determinants and multilocus sequence typing (MLST). Selected six isolates were further analyzed by genomic sequencing and transmission electron microscopy (TEM). Serotype 2 was most prevalent, followed by serotypes 3, 4, 8 and 7. All isolates carried fbpS; 30, 74 and 79 isolates were positive for epf, mrp and sao, respectively. MLST revealed that while widely distributed clonal complexes, such as 1, 16, 25 and 28 circulate in both countries, a significant part of the population is composed of novel singletons. Six isolates, all positive for the capsule in TEM, harbored cps loci differing to a various degree from these previously described, including one with a novel cps locus (putative NCL21). In conclusion, our study provides first molecular data on S. suis from pigs in the Central/Eastern Europe and contributes to a better characterization of diversity of loci responsible for capsule production in this pathogen.

Antimicrobial photodynamic therapy by means of porphycene photosensitizers.

Antimicrobial photodynamic therapy (APDT) is one of the promising tools for bacteria inactivation, which can be considered as an alternative to the common ways of treatment in the era of growing resistance to antibiotics. Presently applied phototherapeutic agents are often based on porphyrins. Porphycenes, isomers of porphyrin, exhibit even better spectral and photophysical properties regarding PDT and have therefore been proposed as photosensitizers in such applications as anticancer and antimicrobial PDT. We compare three different porphycenes in the study of photodestruction of commonly occurring bacteria: Enteroccocus faecalis, Staphylococcus aureus and Staphylococcus epidermidis. Special interest is drawn to the parent, unsubstituted porphycene, a compound which was not tested before in terms of its photosensitizing activity in the biological systems. The results show that two out of three investigated compounds, the parent porphycene and its quadruply substituted derivative, 2,7,12,17-tetrakis(ß-methoxyethyl) exhibit very good ability of bacteria eradication and fulfill the criteria that are commonly required from the APDT photosensitizers. In contrast, 2,7,12,17-tetra-t-butylporphycene, of which the spectral and photophysical characteristics are very similar to those of the parent compound, is not photoactive. This is explained by its inability to penetrate into the bacteria cell. These results demonstrate extreme sensitivity of the photodestruction efficiency to minor structural variations in the photosensitizer.

IL-6 and FAS (CD95) serum level in patients suffering from psoriasis and in relation to the lymphocyte subpopulations.

In the presented study the subpopulations of blood lymphocytes as well as serum concentrations of IL-6 and FAS in 20 patients with psoriasis triggered by infection and 17 healthy controls were analyzed. The flow cytometry technique and ELISA method were used. We detected statistically significant higher serum level of interleukin-6 (IL-6) in patients with active disease and tendency to the lowering of FAS level, although not statistically significant. Analysis of the correlation between the parameters showed that it was close to statistical significance for IL-6 and CD 95, p = 0.06 and R = 0.41. IL-6 level correlated positively with percentage of CD45RO+ cells (p = 0.05, R = 0.28) and negatively with percentage of CD3+ cells (p = 0.02, R = -0.34), CD4+ cells (p = 0.02, R = -0.34), CD 45RA+ cells (p = 0.04, R = -0.68).

New development in the treatment of psoriasis--infliximab.

TNF-alpha may have an impact on principal pathological phenomena in psoriatic skin through inducing inflammatory cells migration from blood vessels. It follows that blockade of TNF-alpha should diminish inflammation and normalize keratinocyte proliferation in psoriasis. Infliximab is a mouse-human chimeric monoclonal antibody that neutralizes the biologic activity of tumor necrosis factor alpha (TNF-alpha) by binding to the soluble and transmembrane forms of this cytokine and inhibiting its binding to the receptors. We present literature data concerning both application of infliximab in patients with psoriasis and its side effects.

[Some genomic aberrations in B-cell chronic lymphocytic leukemia and their clinical relevance. Part II. Trisomy 12 in B-cell chronic lymphocytic leukemia detected by fluorescence in situ hybridization]. / Niektóre aberracje genomu w przewleklej bialaczce limfatycznej B-komórkowej i ich znaczenie kliniczne. Czesc II: Trisomia chromosomu 12 w przewleklej bialaczce limfatycznej B-komórkowej badana technika fluorescencyjnej hybrydyzacji in situ.

Among 75 untreated patients with typical (CD19+, CD5/CD19+, CD23/CD19+) B-cell chronic lymphocytic leukemia (B-CLL) cytogenetic aberrations of peripheral blood cells were evaluated, using fluorescence in situ hybridization techniques. Two cytogenetic aberrations were evaluated: trisomy 12 and TP53 deletion. The clonality was determined when > or = 10% of the cells had of trisomy 12 or deletion TP53 gene. Trisomy 12 in 7 patients was detected, while trisomy 12 and TP53 deletion simultaneously in 6 patients were present. If the first group will be linked to the second one then 13 patients among 75 (17%) will have trisomy 12. In group of patients with trisomy 12 and TP53 deletion percentage of cells with trisomy 12 was almost two time more compare to patients with trisomy 12 as a single aberration. It is possible, that TP53 deletion ("the guardian of the genome") facilitates proliferation clones with others genomic aberrations. In two patients with trisomy 12 control cytogenetic study was performed. Increase of percentage cells with trisomy 12 for 8% and 30% respectively was detected. However, proliferation of cells with TP53 deletion was observed too. Clinical course of B-CLL in group of patient with trisomy 12, trisomy 12 and TP53 deletion simultaneously is more aggressive compared to the course of disease of patients with no cytogenetic aberrations (patients of Group I from Part I of paper). Frequency of IGHV gain mutation occurrence was not analyzed in both groups of patients. But trisomy 12 together with unmutated IGHV gene is found by some authors. The absence IGHV gene mutation is independent unfavourable prognostic factor.